The neural basis of drug craving: An incentive-sensitization theory of addiction

Robinson, Terry E.

doi:10.1016/0165-0173(93)90013-p

Cited by 6,573 publications

(5,539 citation statements)

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“…This curious 'suspiciousness' of the environment later evolves into paranoia and psychotic thought (Ellinwood et al, 1973;Segal et al, 1981;Segal and Schuckit, 1983). Because pretreatment with AMPH facilitates the later acquisition of drug self-administration in rodents (Piazza et al, 1989), it has also been theorized that sensitization may underlie the development of drug craving, and thus initiate addictive behaviors seen in human drug dependence (Robinson and Berridge, 1993).…”

Section: Behavioral Characteristics Of Sensitizationmentioning

confidence: 99%

Behavioral Sensitization, Alternative Splicing, and D3 Dopamine Receptor-Mediated Inhibitory Function

Richtand

2006

Neuropsychopharmacol

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Behavioral sensitization, the progressive and enduring augmentation of certain behaviors following repetitive drug use, alters rodent locomotion in a long-standing manner. The same dopamine pathways playing an important role in drug dependence and psychosis also play a critical role in sensitization. Individual dopamine receptor subtypes have markedly different functional responses to stimulation, with D3 dopamine receptor stimulation inhibiting rodent locomotion. The D3 receptor has highest affinity of the dopamine receptor subtypes for dopamine, and is occupied to a greater degree following stimulant drug administration. D3 receptor activity may be regulated through the expression of an alternatively spliced, truncated receptor isoform (termed 'D3nf') altering receptor localization and function via dimerization with the full-length subunit. The expected physiological response to repetitive drug administration is tolerance. Tolerance of D3 receptor inhibition of locomotion would contribute to sensitization to stimulant drugs. We hypothesize that repetitive D3 receptor stimulation contributes to the development of behavioral sensitization through decreased responsivity of D3-receptor-mediated locomotor inhibition. Increased D3nf expression may direct altered receptor localization and subsequent release of D3-receptormediated inhibition, contributing to the expression of sensitization. These hypotheses follow directly from the affinities of the receptor subtypes for dopamine; dopamine concentrations following stimulant administration; the effects of individual dopamine receptor subtype stimulation on locomotion; and the expected homeostatic response of the system to perturbation by drug. Clarifying these mechanisms underlying sensitization may suggest new interventions for neuropsychiatric conditions in which dopamine plays an important role, including psychosis, drug dependence, and Parkinson's disease. This information may also elucidate a previously unrecognized mechanism regulating receptor trafficking and desensitization.

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Section: Behavioral Characteristics Of Sensitizationmentioning

confidence: 99%

Behavioral Sensitization, Alternative Splicing, and D3 Dopamine Receptor-Mediated Inhibitory Function

Richtand

2006

Neuropsychopharmacol

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“…Several mechanisms may contribute to the association between alcohol and tobacco use, including genes involved in regulating neurotransmitters, cross‐tolerance and cross‐sensitization to both drugs, conditioning mechanisms in which cravings for alcohol or nicotine are elicited by similar environmental cues, and common psychological and social factors (e.g. personality characteristics and psychiatric conditions) 17, 18, 19, 20, 21, 22. Mechanisms proposed for the negative impact of alcohol on smoking cessation include reduced inhibitory control and an increase in the salience of smoking cues 23, 24.…”

Section: Introductionmentioning

confidence: 99%

Association between smoking and alcohol‐related behaviours: a time–series analysis of population trends in England

et al. 2017

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AimsThis paper estimates how far monthly changes in prevalence of cigarette smoking, motivation to quit and attempts to stop smoking have been associated with changes in prevalence of high‐risk drinking, and motivation and attempts to reduce alcohol consumption in England.DesignData were used from the Alcohol and Smoking Toolkit Studies between April 2014 and June 2016. These involve monthly household face‐to‐face surveys of representative samples of ~1700 adults in England.MeasurementsAutoregressive Integrated Moving Average with Exogeneous Input (ARIMAX) modelling was used to assess the association over time between monthly prevalence of (a) smoking and high‐risk drinking; (b) high motivation to quit smoking and high motivation to reduce alcohol consumption; and (c) attempts to quit smoking and attempts to reduce alcohol consumption.FindingsMean smoking prevalence over the study period was 18.6% and high‐risk drinking prevalence was 13.0%. A decrease of 1% of the series mean smoking prevalence was associated with a reduction of 0.185% of the mean prevalence of high‐risk drinking 2 months later [95% confidence interval (CI) = 0.033 to 0.337, P = 0.017]. A statistically significant association was not found between prevalence of high motivation to quit smoking and high motivation to reduce alcohol consumption (β = 0.324, 95% CI = –0.371 to 1.019, P = 0.360) or prevalence of attempts to quit smoking and attempts to reduce alcohol consumption (β = −0.026, 95% CI = –1.348 to 1.296, P = 0.969).ConclusionBetween 2014 and 2016, monthly changes in prevalence of smoking in England were associated positively with prevalence of high‐risk drinking. There was no significant association between motivation to stop and motivation to reduce alcohol consumption, or attempts to quit smoking and attempts to reduce alcohol consumption.

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“…Both psychopharmacological manipulations and lesions of the dopamine system impair reward-driven behaviour of animals 18,21 , and drugs of abuse, which provide strong arti®cial rewards, act via dopamine neurons 19,20 . Neurobiological investigations of associative learning have shown that dopamine neurons respond phasically to rewards in a manner compatible with the coding of prediction errors 22±28 , whereas slower dopamine changes are involved in a larger spectrum of motivating events 18,28,29 .…”

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Dopamine responses comply with basic assumptions of formal learning theory

Waelti

Dickinson

Schultz

2001

Nature

947

749

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According to contemporary learning theories, the discrepancy, or error, between the actual and predicted reward determines whether learning occurs when a stimulus is paired with a reward. The role of prediction errors is directly demonstrated by the observation that learning is blocked when the stimulus is paired with a fully predicted reward. By using this blocking procedure, we show that the responses of dopamine neurons to conditioned stimuli was governed differentially by the occurrence of reward prediction errors rather than stimulus±reward associations alone, as was the learning of behavioural reactions. Both behavioural and neuronal learning occurred predominantly when dopamine neurons registered a reward prediction error at the time of the reward. Our data indicate that the use of analytical tests derived from formal behavioural learning theory provides a powerful approach for studying the role of single neurons in learning.Classic theories assume that predictive learning occurs whenever a stimulus is paired with a reward or punishment 1,2 . However, more recent analyses of associative learning argue that simple temporal contiguity between a stimulus and a reinforcer is not suf®cient for learning and that a discrepancy between the reinforcer that is predicted by a stimulus and the actual reinforcer is also required 3±6 . This discrepancy can be characterized as a`prediction error' 7 . Presentations of surprising or unpredicted reinforcers generate positive prediction errors, and thereby support learning, whereas omissions of predicted reinforcers generate negative prediction errors and lead to reduction or extinction of learned behaviour. Expected reinforcers do not generate prediction errors and therefore fail to support further learning even when the stimulus is consistently paired with the reinforcer. Modelling studies have shown that neuronal messages encoding prediction errors can act as explicit teaching signals for modifying the synaptic connections that underlie associative learning 8±17 .Current research suggests that one of the principal reward systems of the brain involves dopamine neurons 18±21 . Both psychopharmacological manipulations and lesions of the dopamine system impair reward-driven behaviour of animals 18,21 , and drugs of abuse, which provide strong arti®cial rewards, act via dopamine neurons 19,20 . Neurobiological investigations of associative learning have shown that dopamine neurons respond phasically to rewards in a manner compatible with the coding of prediction errors 22±28 , whereas slower dopamine changes are involved in a larger spectrum of motivating events 18,28,29 . Dopamine neurons show short-latency, phasic activations when rewards occur unpredictably, they are not modulated by fully predicted rewards and show phasically reduced activity when predicted rewards are omitted. During initial learning, when rewards occur unpredictably, dopamine neurons are activated by rewards. They gradually lose the response as the reward becomes increasingly predicted 24,25,27 . The co...

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The neural basis of drug craving: An incentive-sensitization theory of addiction

Cited by 6,573 publications

References 307 publications

Behavioral Sensitization, Alternative Splicing, and D3 Dopamine Receptor-Mediated Inhibitory Function

Behavioral Sensitization, Alternative Splicing, and D3 Dopamine Receptor-Mediated Inhibitory Function

Association between smoking and alcohol‐related behaviours: a time–series analysis of population trends in England

Dopamine responses comply with basic assumptions of formal learning theory

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